The proposed research is designed to characterize the molecular mechanism by which heart subcellular membranes may activate the complement system and whether this type of activation of complement may be involved in the evolution of myocardial infarction size following coronary artery occulusion. These studies will include 1) characterization of the subcellular heart fractions (i.e., nuclear, inner and outer mitochondrial, lysosomal, sarcoplasmic reticular and cytosolic) which can initiate the antibody-independent activation of the classicial and/or alternate complement pathways; and 2) delineation of potential therapeutic agents that can inhibit or attenuate such activation. Studies to be comducted in the dog and in man will include correlation of 1) the amount of cardiac damage following myocardial infarction with the in vivo consumption of individual complement components; 2) localization of complement components in heart tissue following acute myocardial infarction; and 3) the effect of various therapeutic agents in decreasing the localization of complement components within heart tissue and the evolution of infarct size by specifically blocking the subcellular membrane-dependent activation of the classical and/or alternate complement pathways.